TRAP1: a viable therapeutic target for future cancer treatments?

Lettini, Giacomo; Maddalena, Francesca; Sisinni, Lorenza; Condelli, Valentina; Matassa, Danilo Swann; Costi, Maria Paola; Daniele, Simona; Esposito, Franca; Landriscina, Matteo

doi:10.1080/14728222.2017.1349755

Cited by 32 publications

(39 citation statements)

References 91 publications

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“…TRAP1 protects cancer cells from hypoxia-induced mitochondrial dysfunction and cell apoptosis during tumor progression, and is a key regulator of mitochondrial bioenergy that assists tumor cells in avoiding death and damage (7). Therefore, TRAP1 is a potential therapeutic target for designing novel anticancer agents (8). Previous studies determined that changes in TRAP1 expression in normal tissues also impact cellular function.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of TRAP1 aggravates injury of H9c2 cardiomyocytes in a hyperglycemic state

Zhang

Zhong

2019

Exp Ther Med

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Diabetic cardiomyopathy increases the risk of heart failure and is one of the major causes of death in patients with diabetes. The present study investigated the expression and function of tumor necrosis factor receptor-associated protein 1 (TRAP1) in cardiomyocytes in a hyperglycemic state. For the in vitro study, H9c2 cells (rat cardiomyoblasts) were treated with normal glucose, high glucose. TRAP1 expression was determined by reverse transcription-quantitative PCR and western blot analysis. Viability of cardiomyocytes was detected using the CellTiter 96 ® AQ ueous One Solution assay. The intracellular reactive oxygen species (ROS) content was detected using a fluorescent 2' ,7'-dichlorodihydrofluorescein diacetate probe, and the change in mitochondrial membrane potential was detected by JC-1 fluorescent staining. Changes in cell viability, ROS content and mitochondrial membrane potential were determined following small interfering (si) RNA-mediated knockdown of TRAP1. Results demonstrated that compared with the normal control group, the expression of TRAP1 in H9c2 cells decreased in the high glucose group which was accompanied by a reduction in mitochondrial membrane potential and cell viability, and increased intracellular ROS production. TRAP1 expression was significantly decreased following TRAP1-siRNA transfection which was accompanied by enhanced ROS production, lower mitochondrial membrane potential and impaired cell viability. In conclusion, the present findings suggested that the decrease in cardiomyocyte TRAP1 expression under high glucose conditions was associated with myocardial injury. It was hypothesized that TRAP1 may have a protective role on cardiomyocytes under high glucose surroundings.

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Section: Introductionmentioning

confidence: 99%

Downregulation of TRAP1 aggravates injury of H9c2 cardiomyocytes in a hyperglycemic state

Zhang

Zhong

2019

Exp Ther Med

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“…Tumor necrosis factor receptor-associated protein 1 (TRAP1) was initially identified by two independent groups by a yeast-based two hybrid system as a novel protein binding the intracellular domain of the type 1 receptor for tumor necrosis factor and as a molecular chaperone for the retinoblastoma protein [58]. This protein shows a conserved protein architecture with high level of similarity to the heat shock protein 90 (HSP90) [59]. However, despite that, TRAP1 and HSP90 do not share the same functions, and show distinct features.…”

Section: The Mitochondrial Chaperone Tumor Necrosis Factor Receptor-amentioning

confidence: 99%

“…As an additional mechanism, the mitochondrial TRAP1 also forms a cytoprotective complex with the mitochondrial isoform of the calcium-binding, antiapoptotic protein Sorcin in colorectal cancer cells [73]. In such a context, TRAP1 is upregulated in drug-resistant colon cancer cells and in paclitaxeland doxorubicin-resistant breast carcinoma cells [59]. TRAP1 interference in different cancer cell lines (e.g.…”

Section: The Mitochondrial Chaperone Tumor Necrosis Factor Receptor-amentioning

confidence: 99%

“…TRAP1 interference in different cancer cell lines (e.g. colorectal and breast cancers), as well as the use of TRAP1dominant negative mutants, sensitizes cells to multiple cell death inducers, ranging from inhibitors of protein synthesis and degradation to endoplasmic reticulum stress inducers and chemotherapeutics agents [59,62]. On the other hand, overexpression of TRAP1 significantly lowers the cytotoxic activity of the mitochondrial complex I inhibitor BAY in BRAF V600E melanoma cells [59].…”

Section: The Mitochondrial Chaperone Tumor Necrosis Factor Receptor-amentioning

confidence: 99%

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Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer

et al. 2020

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Metabolic reprogramming, carried out by cancer cells to rapidly adapt to stress such as hypoxia and limited nutrient conditions, is an emerging concepts in tumor biology, and is now recognized as one of the hallmarks of cancer. In contrast with conventional views, based on the classical Warburg effect, these metabolic alterations require fully functional mitochondria and finely-tuned regulations of their activity. In turn, the reciprocal regulation of the metabolic adaptations of cancer cells and the microenvironment critically influence disease progression and response to therapy. This is also realized through the function of specific stress-adaptive proteins, which are able to relieve oxidative stress, inhibit apoptosis, and facilitate the switch between metabolic pathways. Among these, the molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1), the most abundant heat shock protein 90 (HSP90) family member in mitochondria, is particularly relevant because of its role as an oncogene or a tumor suppressor, depending on the metabolic features of the specific tumor. This review highlights the interplay between metabolic reprogramming and cancer progression, and the role of mitochondrial activity and oxidative stress in this setting, examining the possibility of targeting pathways of energy metabolism as a therapeutic strategy to overcome drug resistance, with particular emphasis on natural compounds and inhibitors of mitochondrial HSP90s.

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“…In the group of identified proteins, there are molecules of TRAP1 Heat shock protein 75 kDa responsible for nucleotide binding, protein folding, response to stress, and apoptosis signaling pathway, [11] likewise a membrane component responsible for protein localization and trafficking VP13A (Vacuolar protein sortingassociated protein 13A). [12] Also, a co-chaperone, which acts as a regulator of the Hsp70 chaperone machinery that may be involved in the processing of ataxia-linked proteins SACS (Sacsin), has been identified in samples interacting with aptamers A26 and A33.…”

Section: Protein Profile Changesmentioning

confidence: 99%

Changes in Protein Glycosylation as a Result of Aptamer Interactions with Cancer Cells

Drabik

Ner‐Kluza

Hartman

et al. 2019

Proteomics Clinical Apps

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Purpose Based on the recent aptamer‐related breast cancer studies, which indicate the therapeutic role of specific oligonucleotide sequences, experiments have been designed in an attempt to unravel the molecular targets of this mechanism. This article describes the study on glycoproteome changes in breast cancer cells as a result of their interactions with aptamers. Experimental design Aberrations in protein glycosylation play an important role in tumorigenesis and influence cancer progression, metastasis, immunoresponse, and chemoresistance, therefore this study is focused on the identification of the alterations in glycan expression on the surface of proteins as a potential and innovative tool for biomedical applications of aptamers in cancer treatment. Results Two proteins, kinesin‐like protein (KI13B) and proliferating cell nuclear antigen (PCNA), have been identified that carry N‐glycan epitopes after conjugation with aptamer sequences. Conclusions and clinical relevance Multiple features of aptamers as an alternative to protein antibodies are utilized for various biomedical applications ranging from biomarker discovery, bioimaging, targeted therapy, drug delivery, and drug pharmacokinetics and biodistribution. Frequently, aptamers bind to their target molecules and modulate their function. Such therapeutic aptamers can modify the biological pathways for treatment of many types of diseases, such as cancer.

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TRAP1: a viable therapeutic target for future cancer treatments?

Cited by 32 publications

References 91 publications

Downregulation of TRAP1 aggravates injury of H9c2 cardiomyocytes in a hyperglycemic state

Downregulation of TRAP1 aggravates injury of H9c2 cardiomyocytes in a hyperglycemic state

Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer

Changes in Protein Glycosylation as a Result of Aptamer Interactions with Cancer Cells

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